Abstract
Owing to the remarkable heterogeneity of gastric cancer (GC), population-level differentially expressed genes (DEGs) identified using case-control comparison cannot indicate the dysregulated frequency of each DEG in GC. In this work, first, the individual-level DEGs were identified for 1,090 GC tissues without paired normal tissues using the RankComp method. Second, we directly compared the gene expression in a cancer tissue to that in paired normal tissue to identify individual-level DEGs among 448 paired cancer-normal gastric tissues. We found 25 DEGs to be dysregulated in more than 90% of 1,090 GC tissues and also in more than 90% of 448 GC tissues with paired normal tissues. The 25 genes were defined as universal DEGs for GC. Then, we measured 24 paired cancer-normal gastric tissues by RNA-seq to validate them further. Among the universal DEGs, 4 upregulated genes (BGN, E2F3, PLAU, and SPP1) and 1 downregulated gene (UBL3) were found to be cancer genes already documented in the COSMIC or F-Census databases. By analyzing protein-protein interaction networks, we found 12 universally upregulated genes, and we found that their 284 direct neighbor genes were significantly enriched with cancer genes and key biological pathways related to cancer, such as the MAPK signaling pathway, cell cycle, and focal adhesion. The 13 universally downregulated genes and 16 direct neighbor genes were also significantly enriched with cancer genes and pathways related to gastric acid secretion. These universal DEGs may be of special importance to GC diagnosis and treatment targets, and they may make it easier to study the molecular mechanisms underlying GC.
Highlights
In 2012, there were 951,600 estimated new cases and 723,100 deaths from gastric cancer (GC) [1]
We previously developed an algorithm, named RankComp, to identify the differentially expressed genes (DEGs) in each cancer tissue by comparing the relative expression orderings (REOs) in cancer tissue to the highly stable REOs predetermined in a large collection of normal tissues [14]
We aimed to identify genes universally dysregulated in GC, which might affect the carcinogenesis of cancer
Summary
In 2012, there were 951,600 estimated new cases and 723,100 deaths from gastric cancer (GC) [1]. The interindividual molecular heterogeneity of GC is a large obstacle to its clinical diagnosis and treatment. Identifying common molecular biomarkers of GC is of particular significance. Various methods, such as SAM [3], limma [4, 5], and RankProd [6], have been used to identify population-level differentially expressed genes (DEGs) between a group of GC tissues and a group of normal controls. The interindividual heterogeneity of DEGs was not considered in these methods. For a given population-level DEG, we cannot know whether it was frequently dysregulated in any particular type of cancer
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